Abstract Lung cancer accounts for 27% of U.S. cancer deaths. The National Lung Screening Trial demonstrated that lung cancer screening (LCS) with low-dose computed tomography (LDCT) reduces lung cancer mortality. Guidelines recommend offering annual LCS accompanied by smoking cessation treatment to high-risk, older individuals. Payers cover LCS for high-risk individuals, and Medicare requires LCS sites to offer smoking cessation to current smokers. Health care systems adopting LCS have a critical new opportunity to deliver tobacco cessation treatment to smokers at a teachable moment. However, an optimal treatment strategy for these long-term, highly dependent smokers undergoing LCS has not yet been determined, and there are challenges to integrating tobacco treatment services into high-volume radiology practices. We propose a hybrid effectiveness-implementation design to examine the development, integration, and implementation of a novel, personalized, English and Spanish language, evidence-based smoking cessation intervention into LCS sites in a large, diverse, integrated health care delivery system, comprised of two networks. To maximize the reach of tobacco treatment, smokers will be offered personalized assistance and outreach at up to 3 time points (LCS test order, scan, and results). We will utilize novel health information technology (IT) platforms to promote patient outreach and access, using technologies like patient portals, informational videos (Vidscrip), and video- conferencing. Guided by the Health Belief and Self Regulation models with a chronic disease management perspective, the multi-component LCS-tailored intervention targets the older, long-term, heavy smokers who will undergo LCS. It provides counseling support and pharmacotherapy (nicotine replacement therapy [NRT]); is personalized to smokers' risk perceptions, readiness to quit, and LCS results; and systematic screening and referral to community-based resources to address social barriers to quitting. A centralized tobacco treatment specialist will deliver the intervention in a series of proactive motivational telephone- or videoconferencing- based sessions to sustain patient engagement. A randomized trial with a factorial design will test 3 intervention components that vary by (1) counseling duration, (2) NRT dose, and (3) systematic screening and referral for social barriers to quitting among 960 current smokers undergoing LCS at 6 screening sites. The primary outcome is biochemically-validated 7-day point-prevalence tobacco abstinence rates at 6 months. Exploratory analyses will identify patient- and LCS-level factors that moderate the relationship between intervention group and smoking outcomes, including socio-demographic characteristics, medical and smoking characteristics, and LCS-related factors (i.e., LCS result, time point of study entry). Guided by the RE-AIM framework, we will conduct a rigorous mixed methods evaluation of the intervention's reach, adoption, implementation (including cost-effectiveness from provider, payer and patient perspectives), and maintenance. Our program could provide health systems nationally with a sustainable model to integrate tobacco treatment into LCS screening.